1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) → 9-Cyclopentyl-N-(5-(4-(2-(((1,1-dimethylethyl)(dimethyl)silyl)oxy)ethyl)-1-piperazinyl)-2-pyridinyl)-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amine

HRID 79153Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 79153
CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CC([O-])(C)C.[Na+].Cl[C:50]1[N:55]=[CH:54][C:53]([N:56]2[CH2:61][CH2:60][N:59]([CH2:62][CH2:63][O:64][Si:65]([C:68]([CH3:71])([CH3:70])[CH3:69])([CH3:67])[CH3:66])[CH2:58][CH2:57]2)=[CH:52][CH:51]=1.[CH:72]1([N:77]2[C:81]3[N:82]=[C:83]([NH2:86])[N:84]=[CH:85][C:80]=3[C:79]3[CH:87]=[CH:88][N:89]=[C:90]([F:91])[C:78]2=3)[CH2:76][CH2:75][CH2:74][CH2:73]1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:72]1([N:77]2[C:81]3[N:82]=[C:83]([NH:86][C:50]4[CH:51]=[CH:52][C:53]([N:56]5[CH2:61][CH2:60][N:59]([CH2:62][CH2:63][O:64][Si:65]([C:68]([CH3:71])([CH3:70])[CH3:69])([CH3:67])[CH3:66])[CH2:58][CH2:57]5)=[CH:54][N:55]=4)[N:84]=[CH:85][C:80]=3[C:79]3[CH:87]=[CH:88][N:89]=[C:90]([F:91])[C:78]2=3)[CH2:73][CH2:74][CH2:75][CH2:76]1

Komponenten

6

Edukt 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 23676156Sodium t-butoxideHCID 582996889-Cyclopentyl-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amineHCID 582997451-(6-Chloro-3-pyridinyl)-4-(2-(((1,1-dimethylethyl)(dimethyl)silyl)oxy)ethyl)-piperazine

Produkt 1

HCID 582997739-Cyclopentyl-N-(5-(4-(2-(((1,1-dimethylethyl)(dimethyl)silyl)oxy)ethyl)-1-piperazinyl)-2-pyridinyl)-8-fluoro-9H-pyrido[4',3':4,5]pyrrolo[2,3-d]pyrimidin-2-amineAusbeute 48,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysator

Reaktionsbedingungen

Temperatur
105 °C

Versuchsvorschrift

To tris(dibenzylideneacetone)dipalladium (0) (0.0289 g, 0.0316 mmol), xantphos (0.0366 g, 0.0632 mmol), NaOtBu (0.0486 g, 0.506 mmol), compound 247 (0.150 g, 0.421 mmol), and compound 245 (0.114 g, 0.421 mmol) was added degassed dioxane (2.0 mL). The reaction vessel was sealed and stirred at 105° C. overnight. The reaction was loaded directly to silica. Silica gel chromatography (gradient elution 1.5 to 5% 2 M methanolic NH3 in DCM) afforded compound 248 (0.120 g, 48.2% yield). 1H NMR (400 MHz, CDCl3) δ 0.09 (s, 6 H) 0.83-1.00 (m, 9 H) 1.75-1.90 (m, 2 H) 2.05-2.25 (m, 4 H) 2.36-2.53 (m, 2 H) 2.63 (br. s., 2 H) 2.75 (br. s., 4 H) 3.22 (br. s., 4 H) 3.82 (br. s., 2 H) 5.54 (quin, J=9.00 Hz, 1 H) 7.38 (dd, J=9.00, 2.74 Hz, 1 H) 7.72 (dd, J=5.09, 3.13 Hz, 1H) 8.00-8.04 (m, 1 H) 8.06 (d, J=2.74 Hz, 1 H) 8.10 (s, 1 H) 8.36 (d, J=9.00 Hz, 1 H) 9.08 (s, 1 H) ppm.

Aufarbeitung

  1. customdegassed dioxane (2.0 mL)
  2. customThe reaction vessel was sealed
  3. washSilica gel chromatography (gradient elution 1.5 to 5% 2 M methanolic NH3 in DCM)

Quellen und Nachweise

ORD-Eintrag
ord-25b5158dd4cd4b8cbfb106d1314fab01
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08841312B2

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